FAO Meeting Report No. PL/1965/10/2
WHO/Food Add/28.65
EVALUATION OF THE HAZARDS TO CONSUMERS RESULTING FROM THE USE OFFUMIGANTS IN THE PROTECTION OF FOOD
The content of this document is the result of the deliberations of the
Joint Meeting of the FAO Committee on Pesticides in Agriculture and
the WHO Expert Committee on Pesticide Residues, which met 15-22 March
19651
Food and Agriculture Organization of the United Nations
World Health Organization
1965
1 Report of the second joint meeting of the FAO Committee on
Pesticides in Agriculture and the WHO Expert Committee on Pesticide
Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65.
METHYL BROMIDE
Compound
Methyl bromide
Chemical name
Methyl bromide
Synonym
Bromomethane
Empirical formula
CH3Br
Structural formulaRelevant physical and chemical properties
Physical state (atmospheric pressure, 20°C): colourless gas
Boiling-point: 3.56°C
Odour: sickly-sweet or musty
Flash point: non-flammable
Solubility:
Water: 1.37 g/100 ml
Organic solvents: infinitely soluble in alcohol and ether
Specific gravity (liquid): 1.73
Specific gravity (gas): 3.27
Uses
Methyl bromide is extensively used for the fumigation of a wide
range of produce including cereals and cereal products, seeds, pulses,
edible nuts, cheese, oil-seeds, dried fruit, cocoa beans, animal
feeding stuffs, spices and tobacco. These commodities may be fumigated
in special gas-tight chambers operating at atmospheric pressure or at
reduced pressures (vacuum fumigation), in sealed warehouses, in barges
or ships' holds, in railway box cars, and under a covering of
gas-proof sheets. Commodities in large bulk, especially cereals, are
treated if there is a means for forced circulation of the gas.
It is also used, generally in chambers, for the fumigation of
fresh fruit and vegetables and of living plants, usually for plant
quarantine purposes.
Methyl bromide is also used for the disinfestation of buildings,
such as warehouses and flour mills and of empty ships' holds. Other
uses include fumigation of soil for control of nematodes in seed beds;
disinfestation of furniture and clothing; and control of wood-boring
insects in buildings, timber and furniture.
Methyl bromide is occasionally used as a component in liquid
grain fumigants, for example with carbon tetrachloride. It is also
used in various mixtures with ethylene dibromide for the fumigation of
stacks of bagged grain and possibly other commodities.
Residues
The amount of the initial sorption and of the residue immediately
after fumigation depends upon the composition and physical character
of the food, the usage and exposure period, the temperature and the
moisture content. The importance of the effect of moisture content is
shown by the results of laboratory tests on wheat fumigated at 2
lb/1000 ft3 for 24 hours at 70°F. Wheat of 9% moisture content showed
a total bromide content of 30 ppm with no airing, 19 ppm after six
hours' airing and 17 ppm after eight days. The corresponding figures
for wheat of 15% moisture content were 99 ppm, 78 ppm, and 77 ppm
(Lindgren et al., 1962).
Sorption is higher when flour itself is fumigated and residues
are correspondingly higher. Residues of about 50 ppm of inorganic
bromide have been found after treatment corresponding to normal
commercial practice (Burns-Brown et al., 1955).
Higher residues can be expected in ground-nuts and other
oil-seeds than in grain and much higher residues after fumigation of
produce such as oil-seed expeller cakes and meals. Residues between
200 and 250 ppm have been found in cotton-seed meal and flake treated
at the high level of 8 lb/1000 ft3 for four days (Thompson, personal
communication, 1964).
The residue of bromide after a single fumigation of cocoa beans
at normal levels is usually around 10 ppm but much larger residues (up
to 150 ppm) have been reported in some commercially fumigated samples
(Turner, 1964).
Immediately after fumigation the residue consists partly of
unchanged methyl bromide and partly of a fixed residne of inorganic
bromide resulting from reaction with the food constituents. The amount
of unchanged methyl bromide is rapidly reduced either by removal
during airing or by continued reaction with the food.
After fumigation of wheat of 12% moisture content at 20°C at a
measured concentration-time product of 340 mg h/l the amounts of
inorganic bromide and undecomposed methyl bromide found one hour after
treatment were 11.5 ppm and 14 ppm. After 24 hours the corresponding
amounts were 12.5 ppm and 1.5 ppm. The residues of inorganic bromide
found in the milled products were: flour 5 ppm, fine offal 30 ppm and
bran 32 ppm (Pest Infestation Laboratory, 1947).
Effect of fumigant on treated crop
Methyl bromide reacts mainly with the protein fraction of
foodstuffs. In wheat the protein fraction was shown to account for 80%
of the decomposition of sorbed fumigant (Bridges, 1955; Winteringham
et al., 1955), the mechanisms being that of methylation, mainly of
nitrogen- and sulfur-containing groups with the formation of N-methyl
derivatives (methylated histidines), dimethyl sulfonium derivatives
and lesser amounts of methoxyl and thiomethoxyl derivatives. The
sulfur-containing derivatives tend to decompose spontaneously,
possibly producing "off" odours. These reactions are not thought
sufficient to reduce the nutritive value of the food (Clegg and Lewis,
1953; Winteringham, 1955).
Wheat flour treated with methyl bromide at normal levels of
dosage was found to produce foreign odours in bread at the time of
removal of loaves from the oven, but these are not likely to be
detected by the consumer and there is no effect on flavour
(Burns-Brown et al., 1961). The effect of repeated fumigation is
cumulative.
When whole wheat was fumigated at a measured concentration-time
product of 340 mg h/l no taint was detected in loaves baked from the
flour produced from the wheat (Pest Infestation Laboratory, 1947).
There was no effect upon the content of riboflavin and nicotinic acid.
BIOLOGICAL DATA
Biochemical aspects
After absorption, methyl bromide appears to be broken down by the
mammalian body, at least in part, for the level of non-volatile
bromide in the blood and tissues rises significantly. There is also
some evidence that volatile bromide, presumably unchanged methyl
bromide, is stored in tissues which are rich in lipoid material. It is
doubtful, however, whether these findings are relevant to the
consideration of the residues to be found in foodstuffs fumigated with
methyl bromide, because in this process as commercially practised no
unchanged methyl bromide persists (von Oettingen, 1946).
1. The fumigantAcute toxicity
For rabbits the minimum acute lethal dose of methyl bromide has
been estimated at 60-65 mg per kg body-weight, when given by
stomach-tube as a solution in olive oil (Dudley et al., 1940).
100 mg/kg of methyl bromide given by stomach-tube as a solution
in olive oil proved to be fatal to rats in five to seven hours (Miller
and Haggard, 1943).
2. The fumigated foodstuffShort-term studiesRat. When an unspecified number of rats was fed on a diet
fumigated with methyl bromide so as to give a residue in the diet
equivalent to 5760 ppm, calculated as bromide, the animals developed
diarrhoea after three weeks and, over eight weeks in all, their weight
gain was slight, their general condition was poor and reproduction
ceased (Dudley et al., 1940).
In a further experiment extending over 16 weeks in which, again,
the number of animals was not disclosed, a residue equivalent to 1304
ppm bromide in the diet gave rise to increased sleepiness, reduced
activity, increased death-rate, decreased weight gain and cessation of
activity. Return to a normal diet then led to complete restoration to
health (Dudley et al., 1940).
A third experiment was carried out with groups each of 36 young
white rats. They were fed on a methyl bromide fumigated diet for 20
weeks. In those receiving the diet in which the residue was equivalent
to 5760 ppm bromide adverse effects were observed - partial limb
paralysis, scaly tails, a form of xerophthalmia, loss of hair, reduced
food intake, inactivity, impaired reproduction and increased
mortality. By contrast, those animals on a diet in which the residue
was equivalent to 206 and 223 ppm bromide remained apparently healthy,
although their weight gain was slightly reduced. Finally, where the
diet was a mixed one containing fresh vegetables, cheese, peanuts, and
dried fruits, in addition to the rat pellets, all fumigated with
methyl bromide at a concentration of 3 lb per 1000 ft3 (48 g/m3) so
that the residue was equivalent to a maximum of 240 ppm calculated as
bromide, no deleterious effects were seen. In all the experiments
there was no significant histopathology (Dudley et al., 1940).
Two groups, each of 25 males and 32 females, were fed for one
year on a modified Sherman diet, previously fumigated with methyl
bromide at the rate of 2 lb and 6 lb respectively per 1000 ft3 (16 g
to 48 g/m3) and having an average bromide content of 262 ppm and 637
ppm. A group of 10 male and 15 female rats was fed the same basic diet
unfumigated but with the addition of 0.1% (i.e., 1000 ppm) sodium
bromide. The control group received the unmodified diet. At the end of
12 months none of the animals showed any evidence of adverse effect in
growth rate, haematological, histopathological, organ weight and
analytical studies (Spencer et al., 1944).
Rabbit. Groups, each of 12 rabbits, were fed for one year on
diets which had been fumigated with methyl bromide for 24 hours. When
the residue was equivalent to 3254 ppm bromide the animals developed a
progressive paralysis and urinary retention and all died within two
weeks. In the others, for which the residue was equivalent to 67 and
75 ppm bromide, there were no abnormalities, apart from a slight
reduction in weight gain and some polydypsia and polyuria. Post
mortem, bronchopneumonia was common in the high dose group and changes
were found in the brain (Dudley et al., 1940).
Dog. Twenty-two beagles of both sexes, in groups of four to
six animals, were fed for one year on methyl bromide fumigated diets.
The residues of 1389, 2975 and 6097 ppm led to a bromide intake of
approximately 35, 75 and 150 mg per kg body-weight daily. Another
group of dogs was given sodium bromide in the diet at the rate of 100
mg per kg body-weight daily of bromide. Lethargy was seen only in
those animals on the high residue intake and there was occasional
salivation and diarrhoea both in this group and that on sodium
bromide. Otherwise the animals remained substantially healthy and,
post mortem, no significant changes were found (Rosenblum et al.,
1960).
Comments on experimental studies reported
No work has been done on the chronic oral toxicity of methyl
bromide as such. However, it is probable that by far the major part,
if not all, of the residue which persists in foodstuffs fumigated with
methyl bromide in accordance with ordinary commercial practice is in
the form of inorganic bromide. If this is so, the safety of treated
products could be assessed simply on the basis of their bromide
content.
The question still remains whether the small interaction that
takes place between the fumigant and the food constituents could lead
to a significant decrease of nutritional value or to the formation of
toxic compounds. The answer to this should be provided by the feeding
studies with animals given a diet which had previously been fumigated.
These experiments have been short-term and covered three species of
animals. From these it is clear that diets fumigated with methyl
bromide at the usual rates adopted commercially had no deleterious
effects on any of the animals. If, however, the attempt is made to
take the maximum no-effect level demonstrated in animals and then to
apply the conventional safety factor of 100 for extrapolation to man,
the resulting permitted bromide level would be extremely low. It
might, indeed, be no more than the natural level of bromides in a
number of foodstuffs (World Health Organization, 1964).
Evaluation
Since nothing is known about the chronic oral toxicity of
unchanged methyl bromide no acceptable daily intake can be assigned to
it as a residue.
To judge by the work on cereal products the interaction of the
compound with the food is unlikely to have hazardous consequences.
The risk to the consumer from the fixed residue of inorganic
bromide could be assessed, if need be, on the basis that the total
daily intake of this ion from all sources should not exceed 10 mg Br
per kg body-weight (World Health Organization, 1964).
Further work required
Chemical nature of the residue in foods other than cereals.
Biochemical studies on the changes produced by methyl bromide in
food.
Long-term studies, at least in rats, with inorganic bromide.
Chronic oral toxicity of methyl bromide.
REFERENCES
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Burns-Brown, W., Coppock, J. B. M., Edwards, G. H., Greer, E. N.,
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p. 324
Burns-Brown, W., Heseltine, H. K., Devlin, J. J. & Greer, E. N. (1961)
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Dudley, H. C., Miller, J. W., Neal, P. A. & Sayer, R. R. (1940) Publ.Hlth Rep. (Wash.), 55, 2251
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